Clinical Trial Finder

Inclusion Criteria:

1. Patient meet one or more of the criteria below: Arm A. 1. Central nervous system tumor that is positive for the H3 K27M mutation (performed in a laboratory with CLIA or equivalent certification); 2. Central nervous system tumor involving the thalamus, hypothalamus, basal ganglia, brainstem, cerebellum, cerebellar peduncle, midline cortex, corpus callosum, pineal region, optic tract, or optic chiasm. Arm B. 3. Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons. H3 K27M status does not have to be known or positive for this arm. 2. Arm A: Patient must have unequivocal radiographic evidence of progressive disease on as defined by RANO criteria or have documented recurrent glioma on diagnostic biopsy. Arm B: Patient are not required to have radiographic or clinical evidence of progressive disease. 3. Arm A: Patient must be at least 90 days from completion of radiotherapy. Arm B: Patient must be at least 14 days from completion of radiotherapy. 4. Patient must be at least 2 years of age. 5. Patient must weigh at least 10kg. 6. From the projected start of scheduled study treatment, the following time periods must have elapsed from prior anti-cancer treatments: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from anti-cancer antibodies (except 21 days for bevacizumab), 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies, and 1 week from devices used to treat cancer. 7. Brain MRI within 21 days prior to start of study drug. 8. Adequate organ and marrow function as defined below: 1. Absolute neutrophil count ≥1,000/mm3 without growth factor use ≤ 7 days prior to treatment (cycle 1 day 1, C1D1) 2. Hemoglobin >8.0 mg/dL without red blood cell transfusion ≤ 3 days prior to C1D1. 3. Total serum bilirubin <1.5 X upper limit of normal (ULN) 4. AST (SGOT)/ALT (SGPT) ≤2 X ULN; ≤ 5 X ULN if there is liver involvement secondary to tumor. 5. Serum creatinine ≤ 1.5 X ULN (OR creatinine clearance ≥ 60 mL/min/1.73 m2) 9. For patients post pubertal: Female patients must agree to use effective contraception while taking ONC201 and for at least 90 days after completion of treatment. Male patients must be surgically sterile or must agree to use effective contraception while taking ONC201 and for at least 90 days after completion of treatment. The decision of effective contraception will be based on the judgment of the principal investigator. 10. Ability to understand a written informed consent document, and the willingness to sign it. Assent will be obtained when appropriate based on the subjects age.

Exclusion Criteria:

1. Qualifies for participation in an ongoing ONC201 or ONC206 clinical trial. 2. Previously or currently participating in an ONC201 clinical trial. 3. Current or planned participation in a study of an investigational agent (including ONC206) or using an investigational device. 4. Evidence of leptomeningeal disease or CSF dissemination of disease. 5. Any known systemic infection that, in the opinion of the investigator, could compromise the safety of the patient, while taking ONC201. 6. Prolongation of QT/QTcF interval (QTc interval >480 milliseconds) using Frederica's QT correction formula on two ECGs separated by at least 48 hours. 7. A history of Torsades de Pointes or heart failure, hypokalemia, or family history of prolonged QT Syndrome. 8. Concomitant use of medication(s) known to prolong the QT/QTc interval